Role of radiosynovectomy in the treatment of rheumatoid arthritis and hemophilic arthropathies
Department of Nuclear Medicine, Radiotherapy and Oncology,
School of Medical Sciences, Universiti Sains Malaysia, Penang, Malaysia
Radiosynovectomy is a novel method of treatment for
several acute and chronic inflammatory joint disorders. A small amount of a
beta-emitting� radionuclide is injected into the affected joint delivering a
radiation dose of 70 to 100 Gy to the synovia. The proliferative tissue is
destroyed, secretion of fluid and accumulation of inflammation causing cellular
compounds stops and the joint surfaces become fibrosed, providing long term
symptom relief. The radionuclides are injected in colloidal form so that they
remain in the synovium and are not transported by lymphatic vessels causing
radiation exposure to other organs. Complete reduction of knee joint swelling
has been seen in above 40% and pain relief in 88% of patients. Wrist, elbow,
shoulder, ankle and hip joints showed significant improvement in 50-60% and
restoration of normal function and long term pain relief has been achieved in
about 70% of small finger joints. In hemophilic arthropathies complete
cessation of bleeding in about 60% and improved mobility in 75% of patients
has been reported. � 2007 Biomedical Imaging and Intervention Journal. All
Keywords: Radiosynovectomy, treatment of hemophilic
arthropathies, radionuclides in rheumatoid arthritis
Joint disorders are relatively common in any society. Among the various forms of arthritis such as rheumatoid arthritis, osteoarthritis, villonodular synovitis, hemophilic arthropathies, psoriatic arthritis, ankylosing spondylitis and gout, acute and chronic rheumatoid arthritis and hemophilic arthropathies are most common, causing long suffering from pain, deformities and disability. It has been estimated that nearly 30 million people in the South East Asian region suffer from rheumatoid arthritis alone
. Conventional long-term treatment with various combinations of drugs
can bring relief in many cases. However, some joints need additional local
therapy. Mostly corticosteroids are injected into the joints to suppress the
inflammatory process localised in the synovium.
In some cases, surgery is also performed. Radiosynovectomy
(also known as radiosynoviorthesis) is a novel method of treatment for such
joints. The concept of radiosynovectomy was reported earlier, but Delbarre et
al. in the year 1968  introduced the term 'radio-synoviorthesis' for the first
time and also reported their clinical experience. Radisynovectomy or
radiosynoviorthesis is defined as the restoration of inflamed and damaged
synovial membrane of the joints after application of radionuclides
(radioisotopes). The beta rays emitted by the radionuclides are used to
effectively control the inflammatory process of the synovial membrane and the
technique is indicated as an alternative therapy to early surgical synovectomy.
The purpose of this article is to describe the method and
assess the impact of this novel technique in the overall management of
rheumatoid arthritis and hemophilic arthropathies.
Magnitude of the problem
Rheumatoid arthritis (RA) is the most common chronic
inflammatory disease of joints. It affect more than 1% of the population. This
disease is more prevalent in women with a preponderance of 3:1 over men. It has
been estimated that in Malaysia 0.22 million patients are suffering from this
disease. It usually starts in fourth and fifth decade of life. However no age
group in spared from this crippling disease. 80% of patients developing the
disease are found to be between 35 to 50 years of age.
The causes of RA are not known, but there is strong
evidence of involvement of cellular and humoral immune systems. This may be
genetically predetermined as the incidence of sero-positive RA is more common
in the population with HLA-DR4 (60%) than in normal controls (15%). It has also
been suggested that RA manifests in response to certain environmental factors,
and hormonal disturbances may play a role but the actual mechanism is not
known. In many cases RA shows a �tumour like proliferation� with rapidly growing
synovial membrane and pannus formation which behaves similar to a locally
Clinically rheumatoid arthritis presents like a chronic
multi-system disease with a variety of systemic manifestations but a
characteristic feature is the persistent inflammatory synovitis. Most commonly
involved joints are proximal inter-phalangeal joints, metacarpophalangeal
joints, wrist and knee joints. In the long run synovial inflammation causes
cartilage destruction, bone erosion and joint deformity with marked functional
Hemophilia is a common bleeding disorder in South East
Asian countries. The incidence is more than 0.01% . More than half of the
patients with this disorder suffer from arthropathy which cripples life at an early
The cause of hemophilia is a deficiency of clotting
factors VIII (Hemophilia A) and IX (Hemophilia B). Inadequate replacement of
factor VIII and IX, lack of patient education, lack of physician education
regarding simple techniques (application of ice or ice packs, immobilisation of
affected joints, use of slings), lack of physiotherapy and lack of new therapy
methods like radiation synovectomy have contributed to the fact that more than
50% of these patients suffer from physical disability and crippling
Principles of the Therapy
Radioactive isotopes which emit beta rays are used for
Radiosynovectomy. The radionuclides� in the form of colloids, on reaching the
joint cavity are recognised as foreign bodies by the outermost cellular layer
of the synovial membrane and are phagocytosed by these cells. Autoradiographic
investigations show that Yttrium-colloids quickly enter the superficial layers
and also to some extent the deeper layers of the synovial membrane but very
little reaches the bones [3, 4]. Due to the selective radiation of the synovial
membrane, there is necrosis of the cells and reduction in the inflammatory
cellular proliferation. Arthroscopic examination shows a reduction in the
number and size of the synovial villi and reduction in the hyperemic reaction [5,
6]. Later there is progressive fibrosis of the synovial stroma, the vessels
and� rarely, mild diffuse damage to the bones of the joint . There is also
prevention of the filtration and reabsorption of the synovial fluid.
There is complete disappearance of the mononuclear
infiltration in the synovial membrane after a few months and the synovial
membrane is fibrosed . Further destruction of the joint cavity otherwise
caused by continuous immunological reactions is prevented. Since the fibrotic
tissue replacing the synovial membrane cannot react to the immunological
stimulation, there is no recurrence of the inflammatory process and a long term
remission is achieved.
The basic understanding of treatment of rheumatoid
arthritis is that it is a systemic disease and therefore, should be treated
systemically.� Radiosynovectomy is indicated when disease modifying therapy has
been given for 6 months and in spite of that some joints are still affected and
any increase of drug dosage may have serious side effects on the patient. Any
exception from these basic principles of treatment can be made only by an
expert in the field and in consultation with rheumatologist, orthopedician or
the surgical rheumatologist. However, if radiosynovectomy is performed early in
course of the disease, the overall result and prognosis of the treated joint
appears to be better. Although best results are obtained in Steinbrocker stage
I and II of the polyarthritis , radiosynovectomy is effective even in the
later stages of the disease. The main indications for radiosynovectomy are:
acute rheumatoid arthritis, chronic polyarthritis, psoriatic arthritis,
anklylosing spondylitis with peripheral joint involvement, pigmented
villonodular synovitis (6 weeks after surgery) haemarthrosis in hemophilia (not
during active bleeding phase) and activated arthrosis or osteoarthritis.
Radionuclides used in radiosynovectomy
In early studies radionuclide gold-198 in colloidal form
was used. However, due to its gamma component leading to unwanted whole body
radiation exposure combined with spread to lymph nodes and liver, it has been
almost� abandoned.� There are a variety of radionuclides available now which
are suitable for radiosynovectomy. The type of radionuclide to be used is
determined by the size of the joint to be treated. The lesser range (weaker)
beta rays are used in smaller joints like Erbium-169 for finger joints.
Similarly the medium range beta rays of Rhenium-186, Phosphorus-32, etc. are used
for larger joints (wrist, elbow, shoulder, ankle and hip joints) while� the
high energy beta rays of Yttrium-90 with tissue penetration of 3 to 11 mm are
used for knee joints. In recent years several other radionuclides like
Holmium-166, Rhenium-188, Samarium-153, etc. have successfully been introduced
It is difficult to exactly determine the required dosage.
The absorbed dose is not only dependent on the type of the radionuclide and the
amount of activity (MBq / mCi) used but also on various other factors like the
size of joint cavity, synovial thickness, distribution of the colloids in the
joint fluid (water, gelatinous or hemorrhagic) and the inflammatory activity of
the joints. A typical dose of 185 MBq (5mCi) of Yttrium (Yt-90) is used for
knee joints. Approximately 100 Gy per 100 gm synovial tissue should be
absorbed, to have optimal effect.
If done properly, no side effects have been observed.
Infection of the joint is very rare (one in 35,000) in comparison to intra-articular
corticosteroid injections. This is because of the intense beta
radiation emitted by the high concentration of radioactive material in the
joint killing all the bacteria. Temporary radiation or crystal synovitis,
thrombosis due to immobilisation and lymphoedema may occur.
Ideally there should be close cooperation with the nuclear
medicine physician, rheumatologist and orthopedician who would consider the
indication and refer the patients for the procedure. It should be ensured that
the basic therapy for rheumatic disease has been given for 6 months and
surgical options for early or late synovectomy, tendon reconstruction (in case
of tendon rupture), nerve decompression, etc. have been taken into
After taking the history and careful clinical examination
of the patient, the risks, side effects and possible complications of the
procedure have to be explained to the patient and a written consent has to be
In addition to the X-ray films of the affected joints, two
more investigations, namely arthrosonography and scintigraphy, may also be
considered to obtain optimal results.
It is sometimes possible to miss the presence of
problematic Baker's cyst of the knee joint during the clinical examination. If
radiosynovectomy of the knee joint with Baker�s cyst is performed, it may lead
to rupture of the cyst as a consequence of inflammatory reaction . This is
a fatal complication and must be avoided. As such Baker�s cyst of the knee
joint with high risk of rupture is taken as a contraindication for
radiosynovectomy. Fortunately Baker�s cyst can be definitely diagnosed by
arthrosonography. In a study of 980 cases of knee joints treated by
radiosynovectomy, Baker�s cyst was detected in 25% of the knee joints . In
the presence of a firm painful Baker�s cyst� it is advisable to aspirate the
cyst under ultrasound guidance and instill cortisone at least three days prior
to radiosynovectomy. So arthrosonography is absolutely necessary prior to radiosynovectomy
of the knee joints. But it may also be required in case of shoulder joint
because it provides information of the condition inside the joint (effusion,
rotator cuff rupture of the shoulder, sub deltoid bursitis etc.) and also about
the peripheral structures (tenosynovitis, enthesitis etc.). These details and
use of an intensifier help to increase the accuracy of intra articular
administration of the radiopharmaceutical.
The usual skeletal scintigraphy is performed 3 hours after
injection of the radiopharmaceutical (usually 99m-Tc MDP / HDP). In soft tissue
scintigraphy, images have to be taken 5 minutes post� injection at a time when
most of the radiopharmaceutical is still in the blood stream and in soft
tissues. The hyperemic areas in synovitis seen as increased concentration of
the radiopharmaceutical are highly suggestive of inflammatory activity at the
joint. This procedure gives fairly accurate information about the polyarticular
involvement and the intensity of synovitis which correlate well with the degree
and the intensity of pain, even months before any radiological changes are seen
in the joint. For example, it is often possible to identify the particular
tendons or joints of the middle foot causing the actual pain to the patient who
sometimes may not be able to pinpoint exactly the site of involvement. The soft
tissue scintigraphic images also help to identify the suitable joints, which
will respond to radiosynovectomy .
Since even a slight extra- articular extravasation of the
radioactive material can lead to tissue necrosis, it is very important to be
perfect in the injection technique. All joints with the exception of knee
joints must be injected only under radiological guidance. A x-ray machine called
C-arm which is otherwise used for various radiological procedures can be used
for the purpose.
In all joints (specially the small finger joints)
arthrographic orientation of the joint space and the ideal position for the
needle placement should be done before starting the procedure.
After the procedure a distribution scintigram of the joint
wherever possible may be performed to document the distribution of the
radionuclide in the joint.
It is advisable to inject a corticosteroid preparation
along with the radio nuclide for following benefits:
- Radiation synovitis with effusion (knee joint) can be avoided.
- The inflammatory component will subside effectively through the
corticosteroid so that the radionuclide therapy can be more effective.
- In the wrist joint, it helps Rhenium (Rh-186) to spread well in the
distally located inter carpal compartments.
- It helps to relieve the patients of the symptoms immediately and thereby
bridge the time till effects of intense radiation from the radionuclide sets
After the radiosynovectomy, the joint should be
immobilised for 48 hours with help of a splint. It will help to prevent the
lymphatic spread and reduce leakage rate if the joint is given rest for about a
It takes up to 3 months to get the full effects of
radiosynovectomy. Symptoms may persist during this period and sometimes there
may also be an effusion which needs to be drained during the follow up after 3
or 4 months. If corticosteroid has been injected simultaneously, patient may
remain free of complaints even during the initial period till the
radiosynovectomy becomes effective.
Result and discussion
A large number of procedures using Yittrium-90 for knee
joints have been performed worldwide. Improvement rates ranging from 40 to 100
% have been reported [23-27]. In two years follow up of patients, knee joint
swellings were reduced almost completely in 38%, pain relief was achieved in 88
% and stretching deficiency corrected in 71% of the cases . Some reports
quote an improvement rate of 85% after 3-4 years . Rhenium (Re-186) is
used for middle sized joints. Good to excellent results are seen in 60-80%
of the cases in hand, elbow, shoulder, ankle and hip joints . Good to very
good results have been reported in 83% of the elbow joints [29, 30].
Erbium (Er-169) is used in small joints of the fingers.
Good to very good results leading to restoration of normal function has been
reported in 54.6% in a study consisting 1261 finger joints [31, 32].
Similar results were reported by Boussiana et al. in a
double blind study conducted involving PIP joints in 35 patients suffering from
chronic polyarthritis who did not respond to intra articular corticosteroid
injections . Good to excellent results were seen in 71.5% of cases in
relation to pain relief and joint mobility 6 months after radiosynovectomy.
After one year� good to excellent results were seen in 79.4% , with no
improvement in 20.6% of cases. The X-ray findings of the joints treated by
radiosynovectomy showed no changes after 1 year as against those in placebo
group (physiological NaCl) which showed reduction in the joint space. In
addition, there was fibrosis and absence of inflammatory changes in those
joints treated with Er-169 whereas persistence of all histological changes of
rheumatoid arthritis was seen in the placebo group .
Since the radionuclides are applied in form of colloids of
appropriate size, they remain mostly within the joints. There is no significant
radiation exposure to other organ or parts of the body. Being beta emitters,
they also don�t pose any radiation to the environment, so the procedure can be
performed on ambulatory patients.
If adequate response has not been achieved or recurrence
of the disease occurs it may be advisable to repeat the procedure, preferably
6 months after the first treatment. Favourable results have been reported after
re-radiosynovectomy of the knee joints in cases of rheumatoid arthritis.
Radiosynovectomy is an effective alternative therapeutic
approach in many conditions needing additional treatment of individual joints.
It has been found to be cost effective in providing long term relief of pain
The number of centres performing radiosynovectomy is
increasing all over the world and reports of new indications like application
in complication of total knee joint prosthesis leading to effusion is
increasingly seen in literature . There is no radiation risk and the
procedure can be performed on an outpatient basis.
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|Received 4 March 2007; received in revised form 14 June 2007; accepted 18 June 2007
Correspondence: Department of Nuclear Medicine, Radiotherapy and Oncology, School of Medical Sciences, Universiti Sains Malaysia. E-mail: email@example.com (Birendra Kishore Das).
Please cite as: Das BK,
Role of radiosynovectomy in the treatment of rheumatoid arthritis and hemophilic arthropathies, Biomed Imaging Interv J 2007; 3(4):e45
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